Cell culturing is an essential step in manufacturing biological products.
Mammalian cells, for example, Chinese hamster ovary (CHO) cells, are often cultured in order to produce therapeutic proteins. Such proteins may include, e.g., monoclonal antibodies (MAbs), erythropoietin (EPO), and interferons. Mammalian cells are also cultured to produce nucleic acids, viruses for use in vaccines, and antibodies. Microbial cells, e.g., bacteria or yeast, are also used for recombinant protein production for use in pharmaceuticals.
In scaling up cultures from the laboratory bench-top bioreactor to larger commercial production bioreactors, it is important to consider some differences in the requirements of mammalian cells and microbial cells, or microbes. In contrast to microbial cells, e.g., mammalian cells lack a tough outer wall. Mammalian cells typically have a diameter of about 10 micrometers (10 μm), whereas most microbial cells are typically only 1 micrometer (1 μm) or less in diameter. The larger size and the lack of a tough outer wall make mammalian cells much more shear-sensitive and fragile than are microbial cells. It is important to ensure that the materials in the bioreactor are adequately and evenly dispersed within a reasonable time period. In order to minimize shearing and protect the fragile cells, bioreactors designed for culturing mammalian cells have impellers that gently mix the cell culture suspension or the suspension of microcarriers with attached cells. In the biotech/pharmaceutical manufacturing industry, “technical transfer,” also referred to as “technology transfer” (hereinafter, “tech transfer”) of a biopharmaceutical process, such as, e.g., cell culturing, from the research or development level, i.e., small-scale production, to large scale, commercial production is generally a complex, costly, and time consuming process.
Difficulties in the tech transfer process are often encountered because the development level process may include many degrees of freedom, whereas the large scale process may require strictly controlled parameters. A small scale process may work well in the laboratory, but may not work well in a larger volume, or scaled-up process. Often a complete process redesign is required upon tech transfer from a small scale volume to a single, larger scale volume. Further, the small scale process may have been developed without using equipment certified for current good manufacturing practices (cGMP) that are essential for commercial production.
Thus, there is an on-going need in biopharmaceutical development and manufacturing for an easily scalable system and process that provide an easy, reliable, and repeatable tech transfer to large scale production with robustness and cGMP compliance, and without the need for substantial re-testing and further development and refinement of the process. The tech transfer often includes the process protocols, documentation, data, stability data, and training in the techniques used in small scale. However, there is often an urgent need for extensive, time-consuming modifications in the small scale protocol in order to achieve a useable protocol for robust, larger scale production processes and systems.